RENAL SENSORY RECEPTOR ACTIVATION BY CALCITONIN-GENE-RELATED PEPTIDE

In anesthetized rats we examined whether calcitonin gene-related pepti de activated renal pelvic sensory receptors and, if so, whether activa tion of renal pelvic calcitonin gene-related peptide receptors contrib utes to the inhibitory renorenal reflex response to renal mechanorecep tor stimulation. Calcitonin gene-related peptide (0.0026, 0.026, 0.26, and 2.6 mu mol/L) administered into the renal pelvis increased ipsila teral afferent renal nerve activity in a concentration-dependent fashi on (32+/-14%, 69+/-19%, 93+/-26%, and 253+/-48% [air P<.01], respectiv ely). The increases in ipsilateral afferent renal nerve activity elici ted by calcitonin gene-related peptide were associated with increases in contralateral urinary sodium excretion. The calcitonin gene-related peptide receptor antagonist human CGRP (h-CGRP) (8-37) (0.01, 0.1, 1. 0, and 10 mu mol/L) decreased the ipsilateral afferent renal nerve act ivity response to renal pelvic administration of calcitonin gene-relat ed peptide (0.26 mu mol/L) in a concentration-dependent fashion (29+/- 4%, 33+/-12%, 76+/-9% [P<.01], and 86+/-13% [P<.01], respectively). In the presence of renal pelvic perfusion with vehicle, an increase in u reteral pressure of 5, 10, and 20 mm Hg increased ipsilateral afferent renal nerve activity by 13+/-7%, 41+/-7% (P<.01), and 95+/-15% (P<.01 ) and contralateral urinary sodium excretion by 8+/-1%, 24+/-4%, and 4 2+/-7% (all P<.05). The ipsilateral afferent renal nerve activity and contralateral natriuretic responses to graded increases in ureteral pr essure (5 to 20 mm Hg) were unaltered by renal pelvic perfusion with h -CGRP (8-37) at 1.0 and 10 mu mol/L. The data suggest that there are s ensory receptors in the renal pelvic area that are responsive to calci tonin gene-related peptide. Activation of these receptors elicits a co ntralateral natriuretic response similar to that produced by renal mec hanoreceptor stimulation. However, activation of renal calcitonin gene -related peptide receptors does not contribute to renal mechanorecepto r activation.